Overexpression of isocitrate dehydrogenase-1R132H enhances the proliferation of A172 glioma cells via aerobic glycolysis

Abstract

Gliomas are the most common type of primary malignancy of the central nervous system. The identification of mutations in the gene encoding isocitrate dehydrogenase-1 (IDH1) represents a key area of investigation in studies on glioma. The IDH1R132H mutation is a heterozygous point mutation, which affects the amino acid arginine at position 132, however, the metabolic importance of this mutation in tumor cell growth remains to be elucidated. In the present study, A172 glioma cell lines stably overexpressing either wild-type IDH1 or IDH1R132H were produced. The results demonstrated that the IDH1R132H mutation enhanced the proliferation of the A172 glioma cells in vitro. Furthermore, IDH1R132H performed this function by elevating the expression levels of hypoxia inducible factor-1α, leading to an increase in the expression levels of the key glycolytic enzymes, glucose transporter 1 and hexokinase 2. Therefore, the metabolism was shifted towards aerobic glycolysis, leading to an increase in glucose uptake and lactate production. These findings demonstrated that the IDH1R132H molecular target was involved in orchestrating the Warburg effect in mutant IDH1R132H glioma cells.